Mesenchymal stromal cells (MSC) are multipotent and self-renewing cells. MSC are studied for their in vivo and in vitro immunomodulatory effects, in the prevention or the treatment of ischemic injury, and ... [more ▼]

Mesenchymal stromal cells (MSC) are multipotent and self-renewing cells. MSC are studied for their in vivo and in vitro immunomodulatory effects, in the prevention or the treatment of ischemic injury, and for their potential properties of tissue or organ reconstruction. Over the last few years, the potential role of MSC in organ transplantation has been studied both in vitro and in vivo, and their properties make them an ideal potential cell therapy after solid organ transplantation. A prospective, controlled, phase 1-2 study has been initiated at the CHU of Liege, Belgium. This study assesses the potential risks and benefits of MSC infusion after liver or kidney transplantation. Even if the preliminary results of this study look promising, solely a prospective, randomized, large scale, phase 3 study will allow the clinical confirmation of the theoretical benefits of MSC in solid organ transplantation. [less ▲]

Thousands of autologous and at less extent allogeneic hematopoietic stem cells (HSC) bags are cryopreserved in France. The majority of autologous HSC grafts are used within a year after collection ... [more ▼]

Thousands of autologous and at less extent allogeneic hematopoietic stem cells (HSC) bags are cryopreserved in France. The majority of autologous HSC grafts are used within a year after collection. However, many bags are still unused and cryopreserved for many years. In France and on a European scale, the ever-growing number of cryopreserved bags represents a real economic health concern. Indeed, the cost of storage is about 100 € per bag and per year. In addition, quality and therapeutic value of these long-term cryopreserved grafts needs to be evaluated. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from its member centers across France. These workshops took place in September 2013 in Lille. In this article, we addressed the issue of the destruction of long-term cryopreserved grafts be them autologous or allogeneic and provide recommendations regarding their destruction. [less ▲]

As for any cell donation, donor safety parameters must be included in the design of cord blood (CB) collection procedures. Until recently, CB donation has been regarded as a relatively safe procedure, and ... [more ▼]

As for any cell donation, donor safety parameters must be included in the design of cord blood (CB) collection procedures. Until recently, CB donation has been regarded as a relatively safe procedure, and practices have evolved from the early stages of CB banking to make reasonable provisions to protect mothers and infant donors from harm linked to CB donation: informed consent, exclusion of complicated pregnancies and deliveries, as well as of pre-term births, non-interference with obstetrical practices, use of trained staff for CB collection, standardized aseptic collection practices, donation limited to single births. Besides, professional standards foresee careful record keeping of clinical side effects that may occur in the course of CB collection. Since 2011 time to cord clamping has become a concern in the light of publications on iron depletion and post natal outcome, including neurological development, and linked to early or late cord clamping at birth. As data show benefits of late clamping in low birth weight infants in terms of anemia and iron stores, it now admitted by professional organizations to delay cord clamping for 1 minute after birth, especially for pre-term births. However, in full term births after uncomplicated pregnancy, that are the target population for CB donation, there is no clear indication to confirm or refute benefits of late clamping. In some countries, sometimes emotional awareness has increased about optimal timing of cord clamping, leading to some resistance to CB donation and to questioning of the harmless reputation of CB donation. CB banking professionals however have not changed their recommendations, leaving up to obstetrical teams the decision to collect or not, after risk benefit assessment. However, CB bankers remain with the duty of providing transparent and up to date information to mothers, as well as of setting up accurate policies regarding informed consent. [less ▲]

Background: In the context of hematopoietic stem cell transplantation (HSCT), mesenchymal stem cells (MSC) have been used to promote engraftment and prevent graft- versus-host-disease. However, in animal ... [more ▼]

Background: In the context of hematopoietic stem cell transplantation (HSCT), mesenchymal stem cells (MSC) have been used to promote engraftment and prevent graft- versus-host-disease. However, in animal models, MSC were shown to cause pulmonary alterations after systemic administration. The impact of MSC infusion on lung function has not been studied in humans. The objective of the study was to investigate the impact of MSC co-infusion on lung function and airway inflammation as well as on the incidence of pulmonary infections and cytomegalovirus (CMV) reactivation after HSCT. Methods: We have prospectively followed 30 patients who underwent unrelated HSCT with MSC co-infusion after non-myeloablative conditioning (NMA). Each patient underwent detailed lung function testing (FEV1, FVC, FEV1/FVC, RV, TLC, DLCO and KCO) and measurement of exhaled nitric oxide before HSCT and 3, 6 and 12 months posttransplant. The incidence of pulmonary infections and CMV reactivation were also monitored. This group was compared with another group of 28 patients who underwent the same type of transplantation but without MSC co-infusion. Results: Lung function tests did not show important modifications over time and did not differ between the MSC and control groups. There was a higher 1-year incidence of infection, particularly of fungal infections, in patients having received a MSC co-infusion. There was no difference between groups regarding the 1-year incidence of CMV reactivation. Conclusions: MSC co-infusion does not induce pulmonary deterioration 1 year after HSCT with NMA conditioning. MSC appear to be safe for the lung but close monitoring of pulmonary infections remains essential. [less ▲]

Objectives: Significant advances have been achieved regarding the knowledge of the immunoregulatory properties of mesenchymal stem cells (MSC). We are currently involved in several clinical protocols ... [more ▼]

Objectives: Significant advances have been achieved regarding the knowledge of the immunoregulatory properties of mesenchymal stem cells (MSC). We are currently involved in several clinical protocols evaluating these properties in different settings including hematopoietic cells or solid organ transplantation, and severe or refractory autoimmune disorders. Considering the large number of ex-vivo expanded cells required for these clinical protocols (MSC dose varies from 1 to 4x10-6 MSC/kg patient per infusion), we evaluated the Quantum® device, a GMPcompliant, functionally closed, automated hollow fiber bioreactor system and compared it with our traditional clinical culture system in flasks. Methods: Primary and pre-enriched MSC expansions were simultaneously conducted in both culture systems and evaluated in terms of expansion rates and compliance with quality specifications and ISCT-release criteria. Due to practical considerations, most of the experiments conducted in the bioreactor (P1 and P2 expansions) used thawed MSC. These were compared with both fresh and thawed MSC expansions in flasks. Results: The Quantum® device reproducibly produced therapeutic MSC doses that fulfill ISCT-release criteria, are sterile, devoid of mycoplasma and endotoxin, have normal karyotypes and demonstrate immunosuppressive and differentiation capacities in vitro. Cells also grew faster in the bioreactor than in flasks during passage P1 (doubling time 40 compared to 56 hours in flasks) and P2 expansions but not during the primary expansion phase (P0). Seeding 20x10-6 thawed P2-preselected cells on the device allowed us to harvest 110-276x10-6 MSC after a 7 day expansion; seeding 50x10-6 cells resulted in 291-334x10-6 MSC harvested. Conclusion: In conclusion, the Quantum® device is an excellent system to produce a clinical dose of MSC but cost-effectiveness varies as a function of the manufacturing strategy in place. For our particular situation, the use of the Quantum device didn't result in a cost saving solution. [less ▲]

Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Despite major advances in the understanding of GVHD pathogenesis, standard GVHD prophylaxis regimens continue to bebased on the combination of a calcineurin inhibitor with an antimetabolite, while first line treatmentsstill relies on high-dose corticosteroids. Further, no second line treatment has emerged thus far in acute or chronic GVHD patients who failed on corticosteroids. After briefly reviewing current standards of GVHD prevention and treatment, this article will discuss recent approaches that might change GVHD prophylaxis / treatment in the next decades, with a special focus on recently developed immunoregulatory strategies based on infusion of mesenchymal stromal or regulatory T-cells, or on injection of lowdose interleukin-2. [less ▲]

Since the early years 1990 when the first cord blood (CB) banks were created, the worldwide inventory has grown considerably to a current 590 thousand units that complement the 22 M donors to provide ... [more ▼]

Since the early years 1990 when the first cord blood (CB) banks were created, the worldwide inventory has grown considerably to a current 590 thousand units that complement the 22 M donors to provide hematopoietic progenitor cells (HPC) to patients in need of an allogeneic transplantation. The existing inventory shows a high degree of heterogeneity with a significant number of units below the current transplantation standards for adult patients. In the mean time, the use of CB as a HPC source has remained steady over the last years, leading to a relative decrease in the release activity in each individual bank. New challenges and innovations have emerged, such as: • More stringent regulations in the USA and in the EU • Upgrades in professional standards • Competing transplantation approaches such as easier access to adult unrelated donors (UD), use of haplo identical donors, single or multiple CB transplantation • CB collection safety becoming a concern since issues have been raised about the outcome of newborns linked to their iron status • The definition of clear criteria for transplant selection (HLA typing level, cell contents) • Potential role of CB banks in non hematological CB use (use of CB byproducts, generation of iPS from selected universal donors, immunotherapy, HIV therapy) • Financial restrictions The elements mentioned above have lead banking strategies, including recruitment, donor selection, CB collection, processing, storage and release to evolve considerably and to incorporate • Active volunteer accreditation processes for international recognition • Donor recruitment: more detailed and selective donor evaluation • Systematic nucleic acid (NAT) testing for infectious disease markers (IDM) • Extensive use of molecular HLA typing and widening range of loci to be taken into account • Evolving definition of acceptance criteria for incoming CB units, (i.e. stricter TNC requirements) • Well standardized processing and storage methods • Evaluation and adaptation of supply vs. needs in strategic approaches • Need to increase and optimize CB visibility through up to date electronic solutions • Methods to have a permanent and up to date overview of post transplantation outcomes, including elements relevant to the banking and clinical side Professional organizations (NetCord, WMDA, FACT, WBMT) are in the process of tightening their links in order to increase interactions and respond in time to upcoming challenges and evolutions of the field. [less ▲]

MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC ... [more ▼]

MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC infusion after cadaveric kidney and liver transplantation in a prospective phase I-II study, taking advantage of our centre expertise and experience in MSC use in graft-versus-host disease (GVHD) after bone marrow transplantation and using an already functioning GMP-compliant laboratory producing clinical-grade MSC. Secondary end-points will help to evaluate the immunosuppressive potential of MSC after organ transplantation, and the opportunity to develop larger randomised, controlled, phase III trials. After successful transplantation, 10 liver and 10 kidney transplant recipients under standard immunosuppression (tacrolimus, MMF, steroids) will receive an intravenous infusion of 1.5-3x106/kg of third-party MSC on post-operative day 3±2. These patients will be prospectively compared to 10 liver and 10 kidney recipients who meet the inclusion criteria but deny MSC infusion. Safety will be assessed by recording side effects, including opportunistic infections and cancers. Immunosuppressive potential will be evaluated by rejection episode rates, by graft/patient survivals, by immunohistology of 3-months kidney and 6-month liver graft biopsies and by in vitro evaluation of the immunity profile of the recipients. In a second step, reduction (kidney) and progressive weaning (liver) of immunosuppression will be attempted in recipients who received MSC. This ongoing study is supported by research grants from the CHU of Liège, University of Liège, and by the Senior Clinical Research Grant from ESOT. The first patients were included and treated in early 2012, and final results expected in late 2013. [less ▲]